Catalysts containing n-heterocyclic carbenes for enantioselective synthesis

ABSTRACT

Novel N-heterocyclic carbene ligand precursors, N-heterocyclic carbene ligands and N-heterocyclic metal-carbene complexes are provided. Metal-carbene complexes comprising N-heterocyclic carbene ligands can be chiral, which are useful for catalyzing enantioselective synthesis. Methods for the preparation of the N-heterocyclic carbene ligands and N-heterocyclic metal-carbene complexes are given.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of U.S. patent application Ser.No. 12/527,635, filed Jan. 20, 2010, which is the U.S. National StageApplication of International Patent Application No. PCT/US2008/054137,filed on Feb. 15, 2008, which claims the benefit of U.S. ProvisionalApplication Ser. No. 60/985,205, filed Nov. 3, 2007, and U.S.Provisional Application Ser. No. 60/890,484, filed Feb. 18, 2007, thedisclosures of which are hereby incorporated by reference herein intheir entirety, including any figures, tables, and drawings.

FIELD OF THE INVENTION

The present invention relates to N-heterocyclic carbene ligands andtransition metal complexes including such ligands. The subject inventionalso relates to catalysts for metal catalyzed and N-heterocyclicorganocatalyzed enantioselective synthesis.

BACKGROUND OF THE INVENTION

When chemical reactions yield chiral compounds, the separation ofenantiomers can be extremely important. In the pharmaceutical industry,for example, oftentimes one enantiomer of a compound provides abeneficial effect while the other enantiomer causes harmful sideeffects. Thus, “single enantiomer” drugs are often highly desirable.

Unfortunately, it is sometimes difficult to obtain a composition thatconsists only of one enantiomer of a chiral compound. For example,because of the similarity of the physical properties of the enantiomers,it can be very difficult to isolate a single enantiomer from a racemicmixture.

One method of producing only one enantiomer is called asymmetricsynthesis, or chiral synthesis. A strategy that is often attempted inasymmetric synthesis is to use a chiral ligand. The ligand complexes tothe starting materials and physically blocks the other trajectory forattack, leaving only the desired trajectory open. This leads toproduction of only one type of enantiomer of the product.

A class of chiral substances that are typical of the prior art is chiralphosphines, in combination with compounds of rhodium or ruthenium. Thesecomplexes work as catalysts for enantioselective synthesis in certaintypes of reactions, including hydrogenation of functionalized alkenes.

Chiral phosphine ligands and their production and use are described in,for example, U.S. Pat. Nos. 7,078,568 and 6,987,202 to Shimizu et al.,U.S. Pat. No. 6,333,291 to Yokozawa et al., U.S. Pat. No. 6,297,387 toAntognazza et al., U.S. Pat. No. 6,172,249 to Berens et al., and U.S.Pat. Nos. 4,397,787 and 4,331,818 to Riley, all of which are herebyincorporated by reference.

These chiral phosphine ligand metal complexes are used for catalysts inthe pharmaceutical industry. Catalysts are very important to speed upand sometimes even initiate chemical reactions. As such, there is alwaysa need for cheaper, cleaner, and more stable catalysts that provide highyields. Specifically, in the context of the current invention, there isa need for catalysts that can be used to promote reactions leading tothe synthesis of a desired single enantiomer compound.

BRIEF SUMMARY OF THE INVENTION

The subject invention provides new and advantageous ligands. The ligandsof the subject invention contain at least two chiral centers and can beresolved into enantionmerically pure forms that can be used to formmetal complexes for catalyzed synthesis, including enantioselectivesynthesis. Specifically exemplified herein are molecules that canprovide one or two N-heterocyclic carbene sites for complexation as aligand. There are two chiral centers common to all N-heterocycliccarbene ligands of the invention at the 9 and10 positions oftrans-9,10-substituted-ethanoanthracene. Thetrans-9,10-substituted-ethanoanthracene portion of the molecule acts asa framework moiety for the disposition of the N-heterocyclic carbeneligands and other ligands or substituents of the N-heterocyclic carbeneligands.

In one embodiment, N-heterocyclic carbene ligands are combined with ametal to form a metal-carbene complex that can include other achiral orchiral ligands. The metal of the metal-carbene complex includetransition metals such as Rh, Ir, Pd, Pt and Ru. The metal-carbenecomplex may be either bimetallic or monometallic, where each metal canhave one or two N-heterocyclic carbenes attached to the metal. The twoN-heterocyclic carbenes of a bis-N-heterocyclic carbene ligand can becomplexed to a single metal or each N-heterocyclic carbene can becomplexed to different metals. The oxidation state of the metal can varyas is appropriate for complexes of the metal as is understood by thoseskilled in the art. One or more anions can be present as counterions tothe metal-carbene complexes.

In another embodiment, a method is provided for the preparation of theN-heterocyclic carbene ligand precursors fromtrans-9,10-substituted-ethanoanthracenes. The method involvetransformations of a trans-9,10-substituted-ethanoanthracene by theaddition to or formation of one or two N-heterocyclic groups. From theseligand precursors the N-heterocyclic carbene ligands can be prepared byreaction with a non-nucleophilic base.

In another embodiment, a method is provided for formation ofmetal-carbene complexes by combining an N-heterocyclic carbene ligandwith a metal salt. The metal salt can be uncomplexed or complexed, andthe resulting metal complex can be a monometallic bis-carbene complex, amonometallic mono-carbene complex or a dimetallic bis-carbene complex,depending on the starting N-heterocyclic carbene ligand and metal.

The N-heterocyclic carbene ligands of the subject invention are lesstoxic, more stable, and potentially less expensive than the currentphosphine ligands. Additionally, the carbene ligands of the presentinvention can be formed in higher yields than phosphine ligands.Moreover, the metal-carbene complexes including the N-heterocycliccarbene ligands of the subject invention can catalyze a wider variety ofreactions than metal complexes containing phosphine ligands.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows the molecular structure oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-di-1-methylbenzimidazoliumtriflate as determined by X-ray crystallography.

FIG. 2 shows the molecular structure of Rhodium (I)trans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidenenorbornadiene triflate as determined by X-ray crystallography.

FIG. 3 shows the molecular structure of [μ²-DEAM-MBY][Rh(COD)Cl]₂ asdetermined by X-ray crystallography.

FIG. 4 shows the molecular structure of Rhodium (I)trans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidene)1,5-cyclooctadiene iodide as determined by X-ray crystallography.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to N-heterocyclic carbene ligandprecursors, N-heterocyclic carbene ligands, metal-carbene complexes fromthese N-heterocyclic carbene ligands, and methods to prepare theN-heterocyclic carbene ligand precursors, N-heterocyclic carbeneligands, and the metal-carbene complexes. The N-heterocyclic carbeneligand precursors, N-heterocyclic carbene ligands, and metal-carbenecomplexes are illustrated within this disclosure as a single enantiomer,however, it is to be understood that the opposite enantiomer and theracemic mixtures of the illustrated enantiomer are also embodiments ofthis invention. Ionic species are herein illustrated as ion pairs, whichare not intended to infer that these ionic species can not exist underthe appropriate conditions as free ions, complexed ions or solvatedions. All of these ionic forms are possible under appropriate conditionsfor the inventive N-heterocyclic carbene ligand precursors andmetal-carbene complexes. Additionally, cations in the N-heterocycliccarbene ligand precursors are generally illustrated as a localized ion,but are generally delocalized cations, as can be appreciated by thoseskilled in the art. Although the N-heterocyclic carbene ligandsaccording to the invention are defined as carbenes, the N-heterocycliccarbene ligand may exist having carbene equivalents, for example, as anenetetramine rather than as formal carbenes, and these equivalent formsare within the definition of a carbene ligand according to theinvention. The N-heterocyclic carbene ligands can exist in solution asformed and used without isolation from reagents and solvent.

These metal-carbene complexes can be used to catalyze a wide variety ofsynthetic transformations, and can be used as catalysts inenantioselective synthesis to generate products with a high enantiomericexcess, in some transformations allowing the isolation of a singleenantiomer of a chiral product. The enantioselective synthesis can beused for the synthesis of optically enriched and optically purecompounds, where the isolation of a pure enantiomer can result in aproduct with superior properties over that of a racemic mixture orpartially resolved mixture of enantiomers, as, for example, in the caseof many pharmaceuticals.

Advantageously, the bis-N-heterocyclic carbene ligands of the subjectinvention are stronger donors of σ-electrons than even the mostelectron-rich phosphines. They are also much less labile than phosphineligands and thus less susceptible to catalyst degradation. TheN-heterocyclic carbene ligands described herein are also less toxic andpotentially less expensive to produce than phosphine ligands, and theycan be electronically and sterically fine-tuned. N-heterocyclic carbeneligands provide a planar environment in a metal complex therefrom, asopposed to the conical environment of typical phosphine ligandscomplexed to a metal.

The N-heterocyclic carbene ligand precursor of the present invention isshown in Formula I:

-   where n is 0 or 1:-   where each R is independently:

-   where at least 1 R is other than NR²R³;-   where R¹, R², and R³ are independently: H; C₁ to C₁₈ straight,    branched, or multiply branched alkyl; benzyl; substituted benzyl;    phenyl; substituted phenyl; napthyl; substituted napthyl; pyridyl;    substituted pyridyl; quinolyl; substituted quinolyl; or    pentafluorobenzyl; and in combination R²R³ can be ═CHR¹; and-   where Z⁻ is Cl⁻, Br⁻, I⁻, PF₆ ⁻, SbF₆ ⁻, ⁻OSO₂CF₃, ⁻OSO₂C₆H₅ or    ⁻OSO₂C₆H₄—R⁴, where R⁴ is an alkylene or oxyalkylene unit bridged    with a polymer or polymeric resin. Substituted, branched, and    multiply branched substituents can be achiral, chiral,    enantiomerically enriched, or racemic. Substitution or branching can    occur at any carbon of the base substituent. The position of    substitution to a multi carbon containing R¹, R², and R³ can be at    any carbon containing an H in the base structure as would be    recognized by one skilled in the art. Substituted can mean mono or    multiply substituted where the substituent can be any alkyl, vinyl,    alkenyl, alkynyl, or aryl group. Any N-heterocyclic carbene ligand    precursor can exist as a racemic mixture, as a partially or totally    resolved enantiomer, or as one or more of multiple possible    diastereomers. Any carbon-hydrogen bond other than that of the    carbon between the two nitrogen atoms of R can be replaced with an    alkylene or oxyalkylene unit bridging the N-heterocyclic carbene    ligand precursor to a polymer or polymeric resin.

In one embodiment, the N-heterocyclic carbene ligand precursor is abis-N-heterocyclic carbene ligand precursor, as shown in Formula II,which is a subset of Formula I where n is 1:

-   where R is independently:

-   where R¹ is: H; C₁ to C₁₈ straight, branched, or multiply branched    alkyl; benzyl; substituted benzyl; phenyl; substituted phenyl;    napthyl; substituted napthyl; pyridyl; substituted pyridyl;    quinolyl; substituted quinolyl; or pentafluorobenzyl; and-   where Z⁻ is Cl⁻, Br⁻, I⁻, PF₆ ⁻, SbF₆ ⁻, ⁻OSO₂CF₃, ⁻OSO₂C₆H₅ or    ⁻OSO₂C₆H₄—R⁴, where R⁴ is an alkylene or oxyalkylene unit bridged    with a polymer or polymeric resin

In another embodiment, the N-heterocyclic carbene ligand precursor is abis-N-heterocyclic carbene ligand precursor, as shown in Formula III,which is a subset of Formula I where n is 0:

-   where R is independently:

-   where R¹ is independently: H; C₁ to C₁₈ straight, branched, or    multiply branched alkyl; benzyl; substituted benzyl; phenyl;    substituted phenyl; napthyl; substituted napthyl; pyridyl;    substituted pyridyl; quinolyl; substituted quinolyl; or    pentafluorobenzyl;-   where Z⁻ is Cl⁻, Br⁻, I⁻, PF₆ ⁻, SbF₆ ⁻, ⁻OSO₂CF₃, ⁻OSO₂C₆H₅ or    ⁻OSO₂C₆H₄—R⁴, where R⁴ is an alkylene or oxyalkylene unit bridged    with a polymer or polymeric resin.

In another embodiment, the N-heterocyclic carbene ligand precursor is amono-N-heterocyclic carbene ligand precursor, as shown in Formula IV,which is a subset of Formula I where n is 0:

-   where R is:

-   where R¹, R², and R³ are independently: H; C₁ to C₁₈ straight,    branched, or multiply branched alkyl; benzyl; substituted benzyl;    phenyl; substituted phenyl; napthyl; substituted napthyl; pyridyl;    substituted pyridyl; quinolyl; substituted quinolyl; or    pentafluorobenzyl, or combined R²R³ can be ═CHR¹; and-   where Z⁻ is Cl⁻, Br⁻, I⁻, PF₆ ⁻, SbF₆ ⁻, ⁻OSO₂CF₃, ⁻OSO₂C₆H₅ or    ⁻OSO₂C₆H₄—R⁴, where R⁴ is an alkylene or oxyalkylene unit bridged    with a polymer or polymeric resin.

The N-heterocyclic carbene ligand precursor can exist as a singleenantiomer or can be used as a racemic mixture, where an N-heterocycliccarbene metal complex ultimately formed from the N-heterocyclic carbeneligand precursor is to be resolved subsequently, or when the chiralproperties of the metal complex are not to be exploited. The singleenantiomer of the N-heterocyclic carbene ligand precursor can beprepared as a single enantiomer or resolved from a racemic mixture.

In one embodiment of the invention the N-heterocyclic carbene ligandprecursor can be attached to a polymer or to a polymeric resin. Anycarbon-hydrogen bond other than that of the carbon between the twonitrogen atoms of R in Formula I can be replaced with an alkylene oroxyalkylene unit bridging the N-heterocyclic carbene ligand precursor toa polymer or polymeric resin. The site of attachment to the polymer orpolymeric resin can be via any site of substitution or branching inFormula I. The trans-9,10-substituted-ethanoanthracenes portion of theN-heterocyclic carbene ligand comprising molecules can be substituted atone or more of the available carbons with a hydrogen substituent on thearomatic rings.

In an embodiment of the invention where the N-heterocyclic carbeneligand precursor is attached to a polymer or to a polymeric resin, thepolymer can be any soluble organic polymer or any cross-linked polymerresin. For example, the polymer can be any organic polymer commonlyprepared by a step-growth or chain-growth mechanism. Exemplary polymersinclude: polystyrenes, polyacrylates, polymethacrylates, polyalkenes,polyesters, polyamides, polyethers, and polysiloxane. Polymeric resinscan be any cross-linked organic polymer including polystyrene resins,acrylic resins, epoxy resins, and fluorocarbon resins. TheN-heterocyclic carbene ligand precursor can be attached by an ionic bondwhere the anion, Z, of Formula I is an ⁻OSO₂C₆H₄—R⁴ group, where R⁴ isan alkylene or oxyalkylene unit bridged to a polymer or polymeric resin.In this manner, a cation exchange resin can be transformed into anN-heterocyclic carbene ligand comprising resin by ion exchange of anN-heterocyclic carbene ligand comprising molecule with a cation bound tothe resin.

A method to synthesize N-heterocyclic carbene ligand precursorscomprises the introducing one or two N-heterocyclic groups to a basecontaining at least two chiral centers but is not a meso compound.Commercially available trans-9,10-dihydro-9,10-ethanoanthracenecompounds can become substituted with one or two N-heterocyclic groupswithout racemization of the 9 and 10 carbons. The introduction of theN-heterocyclic group can be carried out by a substitution reaction withthe formation of a salt by mixing a bis-triflate ester, or other esterthat can act as a good leaving group, fromtrans-9,10-dihydro-9,10-ethanoanthracene-11,12-dimethanol with anN-heterocycle, as is shown below in Example 2, for the reaction with1-methylbenzimidazole. Alternately, the N-heterocyclic groups can beintroduced by the formation of a heterocyclic from atrans-9,10-dihydro-9,10-ethanoanthracene-11,12-diamine by carrying out acyclization reaction involving an amine of thetrans-9,10-dihydro-9,10-ethanoanthracene-11,12-diamine. For example, asis shown below in Example 7, the N-heterocyclic carbene ligand precursoris formed by the cyclization reaction oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-diamine with glyoxalfollowed by ammonium chloride and formaldehyde.

The synthesis can be carried out using a pure enantiomer of the startingtrans-9,10-ethanoanthracene compound in the first step of the syntheticmethod. Alternately, enantiomers of the N-heterocyclic carbene ligandprecursors can be resolved to yield a desired enantionmerically enrichedor pure N-heterocyclic carbene ligand precursor and ultimately anenantionmerically enriched or pure N-heterocyclic metal-carbene complex.Resolution can be by any means, for example, chromatography of theracemic mixture using a chiral solvent and/or a chiral stationary phase.Resolution can be provided by kinetic means, such as in a reaction usingan excess of the trans-9,10-ethanoanthracene compound and a limitingamount of one or more complementary reagents that are chiral or havebeen rendered effectively chiral by association or complexation of thereagent, or conversely the trans-9,10-ethanoanthracene compound, with achiral auxiliary, or by using a chiral solvent to selectively lower theenergy of the ground state or transition state in the reaction of oneenantiomer of the starting material in a synthetic step.

In an embodiment of the invention, a method is given for the synthesisof an N-heterocyclic carbene ligand by the reaction of an N-heterocycliccarbene ligand precursor with a non-nucleophilic base, such as an alkalisalt of a hindered amine. For example, potassium hexamethyldisilazane,as is shown below in Examples 3, for the formation oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidine.

In one embodiment of the invention, the N-heterocyclic carbene ligand isa bis N-heterocyclic carbene as illustrated by Formula V for anenetetramine form or Formula VI as a bis-carbene:

-   where n is 0 or 1;-   where R⁵ is independently:

and

-   where R¹ groups are independently: H; C₁ to C₁₈ straight, branched,    or multiply branched alkyl; benzyl; substituted benzyl; phenyl;    substituted phenyl; napthyl; substituted napthyl; pyridyl;    substituted pyridyl; quinolyl; substituted quinolyl; or    pentafluorobenzyl. The position of substitution to a multi carbon R¹    can be at any carbon containing an H in the base structure as would    be recognized by one skilled in the art. Substituted can mean mono    or multiply substituted where the substituent can be any alkyl,    vinyl, alkenyl, alkynyl, or aryl group. Any N-heterocyclic carbene    ligand can exist as a racemic mixture, as a partially or totally    resolved enantiomer, or as one or more of multiple possible    diastereomers.

In another embodiment of the invention, the N-heterocyclic carbeneligand is a mono N-heterocyclic carbene, as illustrated by Formula VII.

-   where R⁵ is:

and

-   where R¹, R² and R³ groups are independently: H; C₁ to C₁₈ straight,    branched, or multiply branched alkyl; benzyl; substituted benzyl;    phenyl; substituted phenyl; napthyl; substituted napthyl; pyridyl;    substituted pyridyl; quinolyl; substituted quinolyl; or    pentafluorobenzyl. The position of substitution to a multi carbon R¹    can be at any carbon containing an H in the base structure as would    be recognized by one skilled in the art. Substituted can mean mono    or multiply substituted where the substituent can be any alkyl,    vinyl, alkenyl, alkynyl, or aryl group. Any N-heterocyclic carbene    ligand can exist as a racemic mixture, as a partially or totally    resolved enantiomer, or as one or more of multiple possible    diastereomers.

The N-heterocyclic carbene ligand can exist as a short livedintermediate where a metal-carbene complex is formed by a reaction insitu and where no free N-heterocyclic carbene ligand is isolated, orstored unisolated in a reaction mixture. Where mono N-heterocycliccarbene ligands are the intermediate, formation of the carbene andsubsequent formation of the metal-carbene complex is frequently carriedout in this manner.

The N-heterocyclic carbene ligand can be combined with a metal salt toform a metal-carbene complex. The metal-carbene complex can be a metalcomplexed with two N-heterocyclic carbene ligands of abis-N-heterocyclic carbene ligand, a metal complexed with a singleN-heterocyclic carbene ligand of a mono-N-heterocyclic carbene ligand,or two metals complexed to a bis-N-heterocyclic carbene ligand whereeach metal is complexed a single N-heterocyclic carbene. Thecoordination number of the metal can be 4-6. Many embodiments of themetal-carbene complexes of the present invention are directed to a4-coordinate metal.

In one embodiment of the invention the metal-carbene complex is amonometallic bis N-heterocyclic carbene complex, as illustrated byFormula VIII:

-   where n is 0 or 1;-   where R⁵ is independently:

-   where R¹ groups are independently: H₁; C₁ to C₁₈ straight, branched,    or multiply branched alkyl; benzyl; substituted benzyl; phenyl;    substituted phenyl; napthyl; substituted napthyl; pyridyl;    substituted pyridyl; quinolyl; substituted quinolyl; or    pentafluorobenzyl;-   where Z⁻ is Cl⁻, Br⁻, I⁻, PF₆ ⁻, SbF₆ ⁻, ⁻OSO₂CF₃, ⁻OSO₂C₆H₅ or    ⁻OSO₂C₆H₄—R⁴, where R⁴ is an alkylene or oxyalkylene unit bridged    with a polymer or polymeric resin;-   where M is Rh, Ir, Pd, Pt, Ru, or other transition metal; and-   where R⁶ is an ancillary bidentate diene ligand selected from the    group consisting of norbornene, substituted norbornene,    1,5-cyclooctadiene, and substituted 1,5-cyclooctadiene. Substituted,    branched, and multiply branched substituents can be achiral, chiral,    enantionmerically enriched, or racemic. Substitution or branching    can occur at any carbon of the base substituent. The position of    substitution to a multi carbon R¹ can be at any carbon containing an    H in the base structure, as would be recognized by one skilled in    the art. Substituted can mean mono or multiply substituted where the    substituent can be any alkyl, vinyl, alkenyl, alkynyl, or aryl    group. Any N-heterocyclic carbene ligand can exist as a racemic    mixture, as a partially or totally resolved enantiomer, or as one or    more of multiple possible diastereomers.

In another embodiment of the invention the metal-carbene complex is abimetallic bis-N-heterocyclic carbene complex, as illustrated by FormulaIX:

-   where n is 0 or 1;-   R⁵ is independently:

-   where R¹ groups are independently: H; C₁ to C₁₈ straight, branched,    or multiply branched alkyl; benzyl; substituted benzyl; phenyl;    substituted phenyl; napthyl; substituted napthyl; pyridyl;    substituted pyridyl; quinolyl; substituted quinolyl; or    pentafluorobenzyl;-   where the metal M is Rh, Ir, Pd, Pt, Ru, or other transition metal;-   where X is Cl, Br or I; and-   where R⁶ is an ancillary bidentate diene ligand selected from the    group consisting of norbornene, substituted norbornene,    1,5-cyclooctadiene, and substituted 1,5-cyclooctadiene. Substituted,    branched, and multiply branched substituents can be achiral, chiral,    enantionmerically enriched, or racemic and substitution or branching    can occur at any carbon of the base substituent. The position of    substitution to a multi carbon R¹ group can be at any carbon    containing an H in the base structure as would be recognized by one    skilled in the art. Substituted can mean mono or multiply    substituted where the substituent can be any alkyl, vinyl, alkenyl,    alkynyl, or aryl group. Any N-heterocyclic carbene ligand can exist    as a racemic mixture, as a partially or totally resolved enantiomer,    or as one or more of multiple possible diastereomers.

In another embodiment of the invention the metal-carbene complex is amonometallic mono-N-heterocyclic carbene complex, as illustrated byFormula X:

-   where R⁵ is:

-   where R¹, R², and R³ are independently: H; C₁ to C₁₈ straight,    branched, or multiply branched alkyl; benzyl; substituted benzyl;    phenyl; substituted phenyl; napthyl; substituted napthyl; pyridyl;    substituted pyridyl; quinolyl; substituted quinolyl; or    pentafluorobenzyl;-   where Z⁻ is Cl⁻, Br⁻, I⁻, PF₆ ⁻, SbF₆ ⁻, ⁻OSO₂CF₃, ⁻OSO₂C₆H₅ or    ⁻OSO₂C₆H₄—R⁴, where R⁴ is an alkylene or oxyalkylene unit bridged    with a polymer or polymeric resin;-   where the metal M is Rh, Ir, Pd, Pt, Ru, or any other transition    metal; and-   where R⁶ is an ancillary bidentate diene ligand selected from the    group consisting of norbornene, substituted norbornene,    1,5-cyclooctadiene, and substituted 1,5-cyclooctadiene. Substituted,    branched, and multiply branched substituents can be achiral, chiral,    enantionmerically enriched, or racemic and substitution or branching    can occur at any carbon of the base substituent. The position of    substitution to a multi carbon in R¹, R², and R³ can be at any    carbon containing an H in the base structure as would be recognized    by one skilled in the art. Substituted can mean mono or multiply    substituted where the substituent can be any alkyl, vinyl, alkenyl,    alkynyl, or aryl group. Any N-heterocyclic carbene ligand can exist    as a racemic mixture, as a partially or totally resolved enantiomer,    or as one or more of multiple possible diastereomers.

According to an embodiment of the invention, a method to prepare theN-heterocyclic metal-carbene complex involves the combination of theN-heterocyclic carbene ligand, for example as an isolated enetetramineor bis-carbene, with a metal salt, which is typically, but notnecessarily complexed with the ancillary ligand of the resultingN-heterocyclic metal-carbene complex. In another embodiment, noisolation of an N-heterocyclic carbene ligand from the reaction mixturefor its formation from the N-heterocyclic carbene ligand precursor isperformed, and a metal salt is added to the reaction mixture to form theN-heterocyclic metal-carbene complex.

The novel N-heterocyclic metal-carbene complexes are appropriate for useas catalyst for the following types of transformations: hydrogenation ofalkenes; hydrosilation of alkenes; hydroboration of alkenes;hydroamination of alkenes; hydroformylation of alkenes; allylicalkylation; c-c coupling reactions (such as Heck, Suzuki, and Stillereactions), asymmetric aldol condensation; asymmetric diels-alder;kinetic resolution of racemic ketones, 1,4 addition of arylboronic acidto ketones; methoxycarbonylation of alkenes; CO/alkylenecopolymerization; and epoxidation of alkenes. The N-heterocyclicmetal-carbene complexes can promote regioselective as well asenantioselective reactions. For example, the use of a racemicN-heterocyclic metal-carbene complex will not enable the isolation of anenantionmerically enriched product when the reagents are otherwiseachiral, yet can promote a regioselective reaction, for example, in anasymmetric addition to an asymmetric alkene, as in the case of ahydroformylation reaction.

The novel N-heterocyclic carbene ligands, can in themselves act ascatalysts for chemical transformations initiated or promoted bycarbenes. For example, the N-heterocyclic carbene ligands can be used tocatalyze: [3+3] cycloadditions of enals and azomethine imines;asymmetric oxodiene diels alder reactions; benzoin condensations;Stetter reactions; Staudinger reactions; annulations of enals andunsaturated N-sulfonyl ketimines; Aza-Morita-Baylis-Hillman reactions ofcyclic enones with N-tosylaryimines; ring expansion of4-formyl-beta-lactams in syntheses of succinimide derivatives;amidations of esters with amino alcohols; epoxide ring openings;hydroacylations of ketones; and cyanosilylations.

The following examples illustrate procedures for synthesizingN-heterocyclic carbene ligand precursors, N-heterocyclic carbene ligandsand N-heterocyclic metal-carbene complexes according to embodiments ofthe present invention.

EXAMPLES

Although methods and materials that are functionally similar orequivalent to those described herein can be used in the practice ortesting of the present invention, suitable methods and materials aredescribed below. All publications, patent applications, patents, andother references mentioned herein are incorporated by reference in theirentirety. In the case of conflict, the present specification, includingdefinitions, will control. In addition, the particular embodimentsdiscussed below are illustrative only and not intended to be limiting.

Example 1 Synthesis oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-di(methyltriflate)

All glassware was oven-dried overnight before use. To a 250 mL roundbottom with a stir bar, and pyridine (1.21 mL, 15.02 mmol) in drymethylene chloride (100 mL) was addedtrans-9,10-dihydro-9,10-ethanoanthracene-11,12-dimethanol (2.00 g, 7.51mmol) at 0° C. Under argon, triflic anhydride (2.52 mL, 15.02 mmol) wasadded to the stirring solution through a dropping funnel over a 30minute period. After 50 minutes the solution was washed with (3 x 100mL) deionized water. The organic layer was dried over magnesium sulfate,filtered, and then evaporated under reduced pressure. The product wasdried under vacuum for 1 h and then stored at −20° C. giving 3.81 g(95%) oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-di(methyltriflate).

Example 2 Synthesis oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-di-1-methylbenzimidazoliumtriflate

All glassware was oven-dried overnight before use. To a 100 mL roundbottom with a stir bar andtrans-9,10-dihydro-9,10-ethanoanthracene-11,12-dimethyltriflate (3.81 g,7.11 mmol) in dry dimethoxyethane (30 mL) was added1-methylbenzimidazole (1.88 g, 14.23 mmol). The reaction was stirredunder argon at reflux for one hour. A white precipitate formed, whichwas filtered and washed with dimethoxyethane giving 3.26 g (96%) oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-di-1-methylbenzimidazoliumtriflate. The molecular structure oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-di-1-methylbenzimidazoliumtriflate as determined by X-ray crystallography is shown in FIG. 1.

Example 3 Synthesis oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidene

Manipulations were done in a nitrogen-filled glovebox. To a 100 mL roundbottom with a stir bar andtrans-9,10-dihydro-9,10-ethanoanthracene-11,12-di-1-methylbenzimidazoliumtriflate (1.00 g, 2.01 mmol) in THF (30 mL) was added potassiumbis-trimethylsilyl amide (0.80 g, 4.03 mmol in 5 mL THF) at −25° C. Thesolution was stirred for an hour, and then the THF was removed underreduced pressure. The yellow solid was triturated with 5 mL of diethylether, followed by 2×5 mL of pentane. The yellow solid was taken up intoluene and then filter through a fine fritted funnel. The yellowmaterial was washed with THF until a white or nearly white material wasleft on the fitted funnel. The filtrate is removed under reducedpressure to give 0.91 g (91%) oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidene).

Example 4 Synthesis of Rhodium (I)trans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidenenorbornadiene triflate

Manipulations were done in a nitrogen filled glovebox. To a small glassvial with a stir bar and a solution oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidene)(70.0 mg, 0.142 mmol in 5 mL THF) was added a solution of rhodium(I) bisnorbornadiene tetrafluoroborate (50.0 mg, 0.134 mmol in 5 mL THF). Thereaction was stirred overnight. The yellow precipitate that formed wasfiltered through a fine fritted funnel and washed with 2×3 mL of coldTHF to give 95 mg (97%) of Rhodium (I)trans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidenenorbornadiene triflate. The molecular structure of Rhodium (I)trans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidenenorbornadiene triflate as determined by X-ray crystallography is shownin FIG. 2.

Example 5 Synthesis of [μ²-DEAM-MBY][Rh(COD)Cl]₂

To a solution oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidene)(33 mg, 0.067 mmol) in 3 mL THF was added a solution of [Rh(COD)Cl]₂(50.1 mg, 0.134 mmol in 3 mL THF). The reaction was set aside overnightproviding a yellow precipitate. The precipitate was filtered and washedwith 2×3 mL of THF to provide [μ²-DEAM-MBY][Rh(COD)Cl]₂ as a yellowcrystalline solid; yield 97 mg (0.05 mmol, 74%). MS(HR−ESI+): Calc. for[C₅₀H₅₄N₄Cl₂Rh₂]: m/z 951.2124 [M−Cl]⁺, Found m/z 951.2106. Anal. Calc.for C₅₀H₅₄N₄Cl₂Rh₂: C, 60.80%; H, 5.51%; N, 5.67%. Found: C, 60.62%; H,5.98%; N, 5.22%. The molecular structure of [μ²-DEAM-MBY][Rh(COD)Cl]₂ isshown in FIG. 3.

Example 6 Synthesis oftrans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-isopropylbenzimidazolidine-2-ylidene

To a 100 mL flask containing a stirring bar andtrans-9,10-dihydro-9,10-ethanoanthracene-11,12-di-1-isopropylbenzimidazoliumtriflate (1.431 g, 1.68 mmol) in THF (30 mL) was added KN(SiMe₃)₂ (0.692g, 3.47 mmol in 5 mL THF) at −35° C. After stirring the solution forfour hours, the solvent was evaporated to provide a yellow solid and asmall amount of a red residue. The yellow solid was taken up in Et₂O,filtered, triturated with 5 mL of pentane, and then dissolved in 2 mL ofTHF. Additional salts were precipitated by addition of 30 mL of pentaneand filtered. The filtrate was evaporated to providetrans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-isopropylbenzimidazolidine-2-ylideneas a pale yellow solid; yield 354 mg (0.773 mmol, 46%). ¹H NMR (300 MHz,C₆D₆, δ): 7.53 (d, J=6 Hz, 2H, NCCHCHCHCHCN), 7.10-6.88 (m, 12H,NCCHCHCHCHCN and CHCCHCH, overlapping signals), 6.81 (d, J=6 Hz, 2H,NCCHCHCHCHCN), 4.43 (sept, J=6 Hz, 2H, —CH(CH₃)₂), 4.29 (s, CCHC), 3.98(dd, J=15 Hz, J=15 Hz, 2H, —CHH—), 3.85 (dd, J=15 Hz, J=15 Hz, 2H,—CHH—), 2.64 (dd, J=6 Hz, J=6 Hz, —CH₂CH), 1.56 (d, J=6 Hz, 6H,—CH(CH₃)₂), 1.51 (d, J=6 Hz, 6H, —CH(CH₃)₂). ¹³C NMR (75.36 MHz, C₆D₆,δ): 225.59 (s, NCN), 144.50 (s, aromatic), 141.49 (s, aromatic), 136.21(s, aromatic), 135.27 (s, aromatic), 127.33 (s, NCCHCHCHCHCN), 126.71(s, NCCHCHCHCHCN), 126.27 (s, CHCCHCH), 123.99 (s, CHCCHCH), 121.93 (s,CHCCHCH), 121.62 (s, CHCCHCH), 110.79 (s, NCCHCHCHCHCN), 110.52 (s,NCCHCHCHCHCN), 52.74 (s, —CH₃), 49.84 (s, —CH(CH₃)₂), 47.31 (s, CCHC),45.53 (s, —CH₂CH), 23.83 (s, —CH(CH₃)₂), 23.79 (s, —CH(CH₃)₂). GCMS(HRCI+): Calc. for C₃₈H₃₉N₄:m/z 551.3169 [M+H]⁻, Found m/z 551.3218. Asillustrated above in the reaction scheme,trans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-isopropylbenzimidazolidine-2-ylideneappears to exist as the bis-carbene in solution, as a single carbeneresonance is observed downfield at 226 ppm in the ¹³C NMR spectrum andin the solid state as no C—C bond between the NCN carbons of theimidazoles is indicated by x-ray diffraction results.

Example 7 Synthesis of1,1′-(9,10-dihydro-9,10-ethanoanthracene-11,12-diyl)bis(1H-imidazole)and 12-(1H-imidazol-1-yl)-9,10-dihydro-9,10-ethanoanthracen-11-amine

To a solution of trans-9,10-dihydro-9,10-ethanoanthracene-11,12-diamine(3.05 g, 12.9 mmol) in MeOH (20 mL) was added glyoxal (3.0 mL of 40%aqueous solution, 2 equiv, 25.8 mmol). The resulting solution turnedbright yellow and became warm immediately and a light yellow precipitateformed. The mixture was stirred for 16 hours. Additional MeOH (20 mL)was added, followed by solid NH₄Cl (2.76 g, 4 equiv., 51.7 mmol) andHCHO (3.85 mL of 37% solution in water, 4 equiv, 51.7 mmol). Theresulting mixture turned dark orange upon heated at reflux for 4 h.H₃PO₄ (3.54 mL of 85% solution in water, 4 equiv, 51.7 mL) was addedslowly and the resulting mixture was heated at reflux for 16 hours. Themixture was cooled to room temperature and volatiles were removed.Dichloromethane was added and the mixture was basified to pH 14 with 10%NaOH solution. The organic extract was dried over MgSO4, filtered, andconcentrated to an orange solid (3.63 g) consisting of an approximately1:1 ratio of1,1′-(9,10-dihydro-9,10-ethanoanthracene-11,12-diyl)bis(1H-imidazole):12-(1H-imidazol-1-yl)-9,10-dihydro-9,10-ethanoanthracen-11-amine.1,1′-(9,10-Dihydro-9,10-ethanoanthracene-11,12-diyl)bis(1H-imidazole)was separated from12-(1H-imidazol-1-yl)-9,10-dihydro-9,10-ethanoanthracen-11-amine byflash column chromatography on 300 g silica gel, using 5% MeOH in CHCl₃as eluent (R_(f) of12-(1H-imidazol-1-yl)-9,10-dihydro-9,10-ethanoanthracen-11-amine=0.28and Rf of1,1′-(9,10-dihydro-9,10-ethanoanthracene-11,12-diyl)bis(1H-imidazole)=0.23in 9:1 CHCl₃:MeOH) to afford1,1′-(9,10-dihydro-9,10-ethanoanthracene-11,12-diyl)bis(1H-imidazole) asa white solid (1.27 g, 30%) and12-(1H-imidazol-1-yl)-9,10-dihydro-9,10-ethanoanthracen-11-amine as awhite solid (725 mg, 20%).1,1′-(9,10-dihydro-9,10-ethanoanthracene-11,12-diyl)bis(1H-imidazole):¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.49-7.46 (m, 2H, ArH), 7.35-7.24 (m,6H, ArH), 7.09 (dd, 2H, J=J=1.1 Hz, N—CH═NCH═CH), 6.92 (dd, 2H, J=J=1.1Hz, N—CH═NCH═CH), 6.18 (dd, 2H, J=J=1.1 Hz, N—CH═NCH═CH) 4.50 (4H,overlapping singlets for bridge and bridgehead, CH's). ¹³C NMR (75.3MHz, CDCl₃) δ (ppm): 140.39 (N—CH═N), 138.16 and 136.16 (C═C), 129.79 (Caromatic), 127.67 (C aromatic, overlapping signals), 126.63 (Caromatic), 124.32 (N—CH═NCH═CH), 117.10 (N—CH═NCH═CH), 64.67(N—CH—CH—C═), 50.78 (N—CH—CH—C═). HRMS (CIP-CI) calc'd (found) forC₂₂H₁₉N₄ (M+H)⁺ 339.1610 (339.1649).12-(1H-imidazol-1-yl)-9,10-dihydro-9,10-ethanoanthracen-11-amine: ¹H NMR(300 MHz, CDCl₃) δ (ppm): 7.43-7.36 (m, 3H, ArH), 7.27-7.21 (m, 3H,ArH), 7.17-7.15 (m, 2H, ArH), 7.12 (dd, 1H, J=J=1.2 Hz, N—CH═N), 6.88(dd, 1H, J=J=1.2 Hz, N—CH═NCH═CH), 6.14 (dd, 1H, J═J═1.2 HzN—CH═NCH═CH), 4.29 (d, 1H, J=2.4 Hz, NH₂CHCHN), 4.20 (d, 1H, J=2.4 Hz,NCHCH bridgehead), 3.90 (dd, 1H, J=3.6, 2.4 Hz, NH₂CHCHN), 3.30 (dd, 1H,J=3.7, 3.0 Hz, NH₂CHCH bridgehead), 1.48 (2H, NH₂). ¹³C NMR (75.3 MHz,CDCl₃) δ(ppm): 141.7, 140.4, 138.7 and 138.1 (C═C), 136.4 (N—CH═N),129.1 (C aromatic), 127.03 (C aromatic), 126.9 (C aromatic), 126.8 (Caromatic), 126.7 (C aromatic), 126.5 (C aromatic), 126.2 (C aromatic),124.1 (C aromatic), 124.04 (C aromatic), 117.7 (C aromatic), 67.4(NH₂CHCHN), 60.0 (NH₂CHCHN), 53.3 (NCHCH bridgehead), 51.6 (NH₂CHCHbridgehead). HRMS (DIP-CI) calc'd (found) for C₁₉H₁₈N₃ (M+H)⁺ 288.1501(288.1496).

Example 8 Synthesis of1,1′-(9,10-dihydro-9,10-ethanoanthracene-11,12-diyl)bis(3-methyl-1H-imidazol-3-ium)diiodide

1,1′-(9,10-Dihydro-9,10-ethanoanthracene-11,12-diyl)bis(1H-imidazole)(940 mg, 2.78 mmol) was dissolved in anhydrous MeCN (15 mL) in glassampoule fitted with a sealable Teflon stopcock. MeI (700 μL, 4 equiv,11.1 mmol) was added and the flask was evacuated then sealed undervacuum. The flask was shielded from light and was heated in a sand bathat 105° C. for 48 hours. The mixture was cooled to room temperature andthe precipitate was filtered and washed with cold MeCN to yield1,1′-(9,10-dihydro-9,10-ethanoanthracene-11,12-diyl)bis(3-methyl-1H-imidazol-3-ium)diiodide as a beige solid (1.24 g, 72%). ¹H NMR (300 MHz, DMSO-d₆) δ(ppm): 8.93 (s, 2H, N—CH═N), 7.68 (m, 2H, ImH), 7.61 (d, 2H, J=6.9 Hz,ArH), 7.41-7.35 (m, 4H, ArH), 7.30-7.25 (m, 2H, ArH), 6.60 (dd, 2H,J=J=1.5 Hz, ImH), 5.48 (s, 2H, bridge CH's), 5.05 (s, 2H, bridgeheadCH's), 3.82 (s, 6H, NCH₃). ¹³C NMR (75.3 MHz, DMSO-d₆) δ (ppm): 139.1and 137.3 (C═C), 136.7 (N—CH═N), 127.6 (C aromatic), 127.5 (C aromatic),126.3 (C aromatic), 125.5 (C aromatic), 123.6 (N—CH═NCH═CH), 119.7(N—CH═NCH═CH), 63.0 (N—CH—CH—C═), 48.3 (N—CH—CH—C═), 36.1 (NCH₃). HRMS(FIA-ESI) calc'd (found) for C₂₄H₂₄IN₄ (M−I)⁺ 495.1040 (495.1040).

Example 9 Synthesis of Rhodium (I)trans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidene)1,5-cyclooctadiene iodide

KN(TMS)₂ (116 mg, 0.58 mmol) in 5 mL THF was added dropwise to a 5 mLsolution containing1,1′-(9,10-dihydro-9,10-ethanoanthracene-11,12-diyl)bis(1-methylbenzimidazolidine-2-ylidene)diiodide (200 mg, 0.27 mmol) and the combined solutions stirred for 2hours. [Rh(COD)Cl]₂ (68 mg, 0.14 mmol in 5 mL THF) was then addeddropwise to the mixture and the solution stirred for 2.5 hours. A yellowprecipitate formed and was filtered and washed with ether and THF toprovide Rhodium (I)trans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidene1,5-cyclooctadiene iodide as a crystalline solid; yield 90 mg, 0.12mmol, 40%. The molecular structure of Rhodium (I)trans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidene1,5-cyclooctadiene iodide by X-ray crystallography is shown in FIG. 4.

Example 10 Regioselective hydroformylation of styrene

Racemic rhodium (I)trans-9,10-dihydro-9,10-ethanoanthracene-11,12-bis(1-methylbenzimidazolidine-2-ylidenenorbornadiene triflate, as prepared in Example 4, was used as a catalystto hydroformylate styrene with a 100 bar H2/CO gas atmosphere at 50° C.within 24 h. The catalyst loading was 0.01 mol%. The branched product,formed with attachment of the CO alpha to the phenyl group of styrene,was produced in 96% selective. Overall, styrene was converted nearlyquantitatively to the aldehyde products. Similar results were alsoachieved for the hydroformylation of allycycanide and vinyl acetate asindicated in Table 1 below with high regioselectivity and essentiallyquantitative hydroformylation.

TABLE 1 Hydroformylation of Alkenes mol % % H₂/ time % branchedSubstrate catalyst CO (h) conversion isomer

0.1 100 24 >99 96

0.1 100 24 >99 75

0.1 100 24 >99 96

It is to be understood that while the invention has been described inconjunction with the detailed description thereof, the foregoingdescription is intended to illustrate and not limit the scope of theinvention, which is defined by the scope of the appended claims. Otheraspects, advantages, and modifications are within the scope of thefollowing claims.

We claim:
 1. An N-heterocyclic carbene ligand precursor comprising acompound of Formula

wherein n is 0 or 1: wherein R is independently:

wherein at least one R is other than NR²R³; wherein R¹, R², and R³ areindependently: H; C₁ to C₁₈ straight, branched, or multiply branchedalkyl; benzyl; substituted benzyl; phenyl; substituted phenyl; napthyl;substituted napthyl; pyridyl; substituted pyridyl; quinolyl; substitutedquinolyl; or pentafluorobenzyl, or combined R²R³ is =CHR¹, wherein thesubstituent is an alkyl, vinyl, alkenyl, alkynyl, or aryl group; andwherein in Z⁻ is Cl⁻, Br⁻, I⁻, PF₆ ⁻, SbF₆ ⁻, ⁻OSO₂CF₃, ⁻OSO₂C₆H₅ or⁻OSO₂C₆H₄—R⁴, where R⁴ is an alkylene or oxyalkylene unit bridged with apolymer or polymeric resin.
 2. The N-heterocyclic carbene ligandprecursor of claim 1, wherein said compound of Formula (I) comprises aracemic mixture, an enantiomerically enriched compound, or anenantiomerically pure compound.
 3. The N-heterocyclic carbene ligandprecursor of claim 1, wherein said compound of Formula (I) is abis-N-heterocyclic carbene ligand precursor wherein n is 1 and R isother than NR²R³.
 4. The N-heterocyclic carbene ligand precursor ofclaim 3, wherein R is


5. The N-heterocyclic carbene ligand precursor of claim 1, wherein saidcompound of Formula (I) is a bis-N-heterocyclic carbene ligand precursorwherein n is 0 and R is other than NR²R³.
 6. The N-heterocyclic carbeneligand precursor of claim 5, wherein R is


7. The N-heterocyclic carbene ligand precursor of claim 1, wherein saidcompound of Formula (I) is a mono-N-heterocyclic carbene ligandprecursor wherein n is 0 and one R is NR²R³.
 8. The N-heterocycliccarbene ligand precursor of claim 7, wherein one R is


9. The N-heterocyclic carbene ligand precursor of claim 1, wherein acarbon-hydrogen bond other than that of the carbon between the twonitrogens of R is replaced with an alkylene or oxyalkylene unit bridgedwith a polymer or polymeric resin.
 10. A method of making anN-heterocyclic carbene ligand precursor according to claim 1 comprisingthe steps of: providing a trans-9,10-dihydro-9,10-ethanoanthracenecompound; and transforming said trans-9,10-dihydro-9,10-ethanoanthracenecompound into said N-heterocyclic carbene ligand precursor.
 11. Themethod of claim 10, wherein saidtrans-9,10-dihydro-9,10-ethanoanthracene compound is an ester derivedfrom trans-9,10-dihydro-9,10-ethanoanthracene-11,12-dimethanol andwherein said step of transforming comprises performing at least onesubstitution reaction with at least one N-heterocycle.
 12. The method ofclaim 11, wherein said ester is a triflate ester.
 13. The method ofclaim 10, wherein said trans-9,10-dihydro-9,10-ethanoanthracene compoundis trans-9,10-dihydro-9,10-ethanoanthracene-11,12-diamine and whereinsaid step of transforming comprises performing at least one cyclizationreaction involving at least one amine of saidtrans-9,10-dihydro-9,10-ethanoanthracene-11,12-diamine.
 14. A method oftransforming an N-heterocyclic carbene ligand precursor of claim 1 intoan N-heterocyclic carbene ligand comprising the step of reacting saidN-heterocyclic carbene ligand precursor with an alkali salt of ahindered amine.
 15. The method of claim 14 wherein said alkali salt of ahindered amine is potassium hexmethyldisilazane.
 16. An N-heterocycliccarbene ligand prepared according to the method of claim 14, comprisinga compound of either Formula V, Formula VI, or Formula VII

wherein: n is 0 or 1; wherein R⁵ is independently:

and wherein R¹ groups are independently: H; C₁ to C₁₈ straight,branched, or multiply branched alkyl; benzyl; substituted benzyl;phenyl; substituted phenyl; napthyl; substituted napthyl; pyridyl;substituted pyridyl; quinolyl; substituted quinolyl; orpentafluorobenzyl, wherein the substituent is an alkyl, vinyl, alkenyl,alkynyl, or aryl group.